Here's how LINK.SPRINGER.COM makes money* and how much!

*Please read our disclaimer before using our estimates.
Loading...

LINK . SPRINGER . COM {}

  1. Analyzed Page
  2. Matching Content Categories
  3. CMS
  4. Monthly Traffic Estimate
  5. How Does Link.springer.com Make Money
  6. Keywords
  7. Topics
  8. Schema
  9. External Links
  10. Analytics And Tracking
  11. Libraries
  12. CDN Services

We are analyzing https://link.springer.com/article/10.1007/s00401-015-1429-9.

Title:
Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy | Acta Neuropathologica
Description:
GGGGCC repeat expansions of C9ORF72 represent the most common genetic variant of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We and others have proposed that RNA transcribed from the repeat sequence is toxic via sequestration of RNA-binding factors. Both GGGGCC-repeat (sense) and CCCCGG-repeat (antisense) molecules are detectable by fluorescence in situ hybridisation as RNA foci, but their relative expression pattern within the CNS and contribution to disease has not been determined. Blinded examination of CNS biosamples from ALS patients with a repeat expansion of C9ORF72 showed that antisense foci are present at a significantly higher frequency in cerebellar Purkinje neurons and motor neurons, whereas sense foci are present at a significantly higher frequency in cerebellar granule neurons. Consistent with this, inclusions containing sense or antisense derived dipeptide repeat proteins were present at significantly higher frequency in cerebellar granule neurons or motor neurons, respectively. Immunohistochemistry and UV-crosslinking studies showed that sense and antisense RNA molecules share similar interactions with SRSF2, hnRNP K, hnRNP A1, ALYREF, and hnRNP H/F. Together these data suggest that, although sense and antisense RNA molecules might be expected to be equally toxic via their shared protein binding partners, distinct patterns of expression in various CNS neuronal populations could lead to relative differences in their contribution to the pathogenesis of neuronal injury. Moreover in motor neurons, which are the primary target of pathology in ALS, the presence of antisense foci (χ 2, p < 0.00001) but not sense foci (χ 2, p = 0.75) correlated with mislocalisation of TDP-43, which is the hallmark of ALS neurodegeneration. This has implications for translational approaches to C9ORF72 disease, and furthermore interacting RNA-processing factors and transcriptional activators responsible for antisense versus sense transcription might represent novel therapeutic targets.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

  • Science
  • Education
  • Music

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
However, some sources were not loaded, we suggest to reload the page to get complete results.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Link.springer.com Make Money? {💸}

We can't tell how the site generates income.

Some websites aren't about earning revenue; they're built to connect communities or raise awareness. There are numerous motivations behind creating websites. This might be one of them. Link.springer.com might be earning cash quietly, but we haven't detected the monetization method.

Keywords {🔍}

rna, foci, neurons, antisense, sense, motor, pubmed, article, repeat, corf, hnrnp, nuclear, cases, google, scholar, proteins, frequency, granule, neuronal, tdp, cerebellar, inclusions, cas, table, central, distribution, protein, observed, purkinje, populations, supplementary, fig, corfals, higher, examined, disease, patients, significantly, dprs, study, srsf, alyref, binding, subfield, polyga, shown, acta, molecules, present, derived,

Topics {✒️}

article cooper-knock chromosome 9p21-linked als-ftd large scale view amyotrophic lateral sclerosis article download pdf chromosome 9p-linked ftd formalin fixed paraffin-embedded aggregating dipeptide-repeat proteins uv-crosslinking studies confirmed likelihood-ratio test revealed depth clinico-pathological examination ipsc-derived motor neurons interacting rna-processing factors dipeptide repeat protein post-mitotic mature cells represents end-stage disease rna fish probes als/ftd c9orf72 expansion repeat rna sequences uv-crosslinking studies showed cell-specific transcriptional regulation secondary structures mackenzie ir antisense/sense repeat sequence hexanucleotide repeat expansion dipeptide repeat proteins rna-binding activity national research committee privacy choices/manage cookies conducted extensive immunohistochemistry donnelly cj c9orf72 repeat expansions ftd cases including antisense repeat rnas c9orf72-related disease original author intra molecular interactions medical research council protein binding partners full access myotonic dystrophy type rna-binding factors rna recognition motif c9orf72 repeat expansion c9orf72 ggggcc repeat antisense repeat rna author information authors uv-crosslinking studies clinico-pathological correlations common genetic variant

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy
         description:GGGGCC repeat expansions of C9ORF72 represent the most common genetic variant of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We and others have proposed that RNA transcribed from the repeat sequence is toxic via sequestration of RNA-binding factors. Both GGGGCC-repeat (sense) and CCCCGG-repeat (antisense) molecules are detectable by fluorescence in situ hybridisation as RNA foci, but their relative expression pattern within the CNS and contribution to disease has not been determined. Blinded examination of CNS biosamples from ALS patients with a repeat expansion of C9ORF72 showed that antisense foci are present at a significantly higher frequency in cerebellar Purkinje neurons and motor neurons, whereas sense foci are present at a significantly higher frequency in cerebellar granule neurons. Consistent with this, inclusions containing sense or antisense derived dipeptide repeat proteins were present at significantly higher frequency in cerebellar granule neurons or motor neurons, respectively. Immunohistochemistry and UV-crosslinking studies showed that sense and antisense RNA molecules share similar interactions with SRSF2, hnRNP K, hnRNP A1, ALYREF, and hnRNP H/F. Together these data suggest that, although sense and antisense RNA molecules might be expected to be equally toxic via their shared protein binding partners, distinct patterns of expression in various CNS neuronal populations could lead to relative differences in their contribution to the pathogenesis of neuronal injury. Moreover in motor neurons, which are the primary target of pathology in ALS, the presence of antisense foci (χ 2, p < 0.00001) but not sense foci (χ 2, p = 0.75) correlated with mislocalisation of TDP-43, which is the hallmark of ALS neurodegeneration. This has implications for translational approaches to C9ORF72 disease, and furthermore interacting RNA-processing factors and transcriptional activators responsible for antisense versus sense transcription might represent novel therapeutic targets.
         datePublished:2015-05-06T00:00:00Z
         dateModified:2015-05-06T00:00:00Z
         pageStart:63
         pageEnd:75
         sameAs:https://doi.org/10.1007/s00401-015-1429-9
         keywords:
             C9ORF72
            Amyotrophic lateral sclerosis
            RNA foci
            Dipeptide repeat protein
            Immunohistochemistry
            Pathology
            Neurosciences
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig1_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig2_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig3a_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig3b_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig3c_HTML.jpg
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig4_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig5_HTML.jpg
         isPartOf:
            name:Acta Neuropathologica
            issn:
               1432-0533
               0001-6322
            volumeNumber:130
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Springer Berlin Heidelberg
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Johnathan Cooper-Knock
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Adrian Higginbottom
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Matthew J. Stopford
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:J. Robin Highley
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Paul G. Ince
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Stephen B. Wharton
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Stuart Pickering-Brown
               affiliation:
                     name:University of Manchester
                     address:
                        name:Institute of Brain, Behaviour and Mental Health, 2.014 AV Hill Building, University of Manchester, Manchester, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Janine Kirby
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Guillaume M. Hautbergue
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Pamela J. Shaw
               affiliation:
                     name:University of Sheffield
                     address:
                        name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
         isAccessibleForFree:1
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy
      description:GGGGCC repeat expansions of C9ORF72 represent the most common genetic variant of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We and others have proposed that RNA transcribed from the repeat sequence is toxic via sequestration of RNA-binding factors. Both GGGGCC-repeat (sense) and CCCCGG-repeat (antisense) molecules are detectable by fluorescence in situ hybridisation as RNA foci, but their relative expression pattern within the CNS and contribution to disease has not been determined. Blinded examination of CNS biosamples from ALS patients with a repeat expansion of C9ORF72 showed that antisense foci are present at a significantly higher frequency in cerebellar Purkinje neurons and motor neurons, whereas sense foci are present at a significantly higher frequency in cerebellar granule neurons. Consistent with this, inclusions containing sense or antisense derived dipeptide repeat proteins were present at significantly higher frequency in cerebellar granule neurons or motor neurons, respectively. Immunohistochemistry and UV-crosslinking studies showed that sense and antisense RNA molecules share similar interactions with SRSF2, hnRNP K, hnRNP A1, ALYREF, and hnRNP H/F. Together these data suggest that, although sense and antisense RNA molecules might be expected to be equally toxic via their shared protein binding partners, distinct patterns of expression in various CNS neuronal populations could lead to relative differences in their contribution to the pathogenesis of neuronal injury. Moreover in motor neurons, which are the primary target of pathology in ALS, the presence of antisense foci (χ 2, p < 0.00001) but not sense foci (χ 2, p = 0.75) correlated with mislocalisation of TDP-43, which is the hallmark of ALS neurodegeneration. This has implications for translational approaches to C9ORF72 disease, and furthermore interacting RNA-processing factors and transcriptional activators responsible for antisense versus sense transcription might represent novel therapeutic targets.
      datePublished:2015-05-06T00:00:00Z
      dateModified:2015-05-06T00:00:00Z
      pageStart:63
      pageEnd:75
      sameAs:https://doi.org/10.1007/s00401-015-1429-9
      keywords:
          C9ORF72
         Amyotrophic lateral sclerosis
         RNA foci
         Dipeptide repeat protein
         Immunohistochemistry
         Pathology
         Neurosciences
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig1_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig2_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig3a_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig3b_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig3c_HTML.jpg
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig4_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00401-015-1429-9/MediaObjects/401_2015_1429_Fig5_HTML.jpg
      isPartOf:
         name:Acta Neuropathologica
         issn:
            1432-0533
            0001-6322
         volumeNumber:130
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Springer Berlin Heidelberg
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Johnathan Cooper-Knock
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Adrian Higginbottom
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Matthew J. Stopford
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:J. Robin Highley
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Paul G. Ince
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Stephen B. Wharton
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Stuart Pickering-Brown
            affiliation:
                  name:University of Manchester
                  address:
                     name:Institute of Brain, Behaviour and Mental Health, 2.014 AV Hill Building, University of Manchester, Manchester, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Janine Kirby
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Guillaume M. Hautbergue
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Pamela J. Shaw
            affiliation:
                  name:University of Sheffield
                  address:
                     name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:1
["Periodical","PublicationVolume"]:
      name:Acta Neuropathologica
      issn:
         1432-0533
         0001-6322
      volumeNumber:130
Organization:
      name:Springer Berlin Heidelberg
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Manchester
      address:
         name:Institute of Brain, Behaviour and Mental Health, 2.014 AV Hill Building, University of Manchester, Manchester, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
      name:University of Sheffield
      address:
         name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Johnathan Cooper-Knock
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:Adrian Higginbottom
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:Matthew J. Stopford
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:J. Robin Highley
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:Paul G. Ince
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:Stephen B. Wharton
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:Stuart Pickering-Brown
      affiliation:
            name:University of Manchester
            address:
               name:Institute of Brain, Behaviour and Mental Health, 2.014 AV Hill Building, University of Manchester, Manchester, UK
               type:PostalAddress
            type:Organization
      name:Janine Kirby
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:Guillaume M. Hautbergue
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      name:Pamela J. Shaw
      affiliation:
            name:University of Sheffield
            address:
               name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Institute of Brain, Behaviour and Mental Health, 2.014 AV Hill Building, University of Manchester, Manchester, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
      name:Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK

External Links {🔗}(154)

Analytics and Tracking {📊}

  • Google Tag Manager

Libraries {📚}

  • Clipboard.js
  • Prism.js

CDN Services {📦}

  • Crossref

4.08s.